rs4240803

chr16-87855597-G-Achr16-87855597-G-Cchr16-87855597-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003486.7(SLC7A5):c.539-3748C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,718 control chromosomes in the GnomAD database, including 9,538 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (9538 hom., cov: 32)
• Consequence: SLC7A5 NM_003486.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

Genes affected

SLC7A5 (HGNC:11063): (solute carrier family 7 member 5) Enables L-leucine transmembrane transporter activity; L-tryptophan transmembrane transporter activity; and thyroid hormone transmembrane transporter activity. Involved in carboxylic acid transport; thyroid hormone transport; and xenobiotic transport. Located in cytosol; intracellular membrane-bounded organelle; and plasma membrane. Is integral component of membrane. Part of amino acid transport complex; apical plasma membrane; and microvillus membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A5	NM_003486.7	c.539-3748C>T		intron_variant		ENST00000261622.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A5	ENST00000261622.5	c.539-3748C>T		intron_variant		1	NM_003486.7	P1
SLC7A5	ENST00000565644.5	c.-260-3748C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51611 AN: 151600 Hom.: 9521 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.345

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.341 AC: 51661 AN: 151718 Hom.: 9538 Cov.: 32 AF XY: 0.353 AC XY: 26138 AN XY: 74096

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.346

Alfa AF: 0.301 Hom.: 11179

Bravo AF: 0.349

Asia WGS AF: 0.531 AC: 1845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.8
Dann	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4240803; hg19: chr16-87889203; COSMIC: COSV55366222;